KR100932531B1 - Potassium organotrifluoroborate derivatives and preparation method thereof - Google Patents

Abstract

The present invention relates to a method for preparing a potassium organotrifluoroborate compound having a hydroxy group and a novel potassium organotrifluoroborate compound having a hydroxy group.

The production method according to the present invention has the advantage of preparing a potassium organotrifluoroborate compound in a single reaction without undergoing the process of separating and purifying the intermediate, and novel potassium organotrifluoro having a hydroxy group according to the present invention. Potassium organotrifluoroborate compounds include Suzuki carbon-carbon coupling reaction using palladium (Pd) catalysts, 1,2- and 1,4-addition reactions using rhodium (Rh) catalysts, and halogen substitution reactions. It is useful as a reactant widely used in organic synthesis and total synthesis of physiologically active natural products.

Potassium Organotrifluoroborate, Suzuki Carbon-Carbon Bonding Reaction

Description

Potassium organotrifluoroborate derivative and its manufacturing method {POTASSIUM ORGANOTRIFLUOROBORATE DERIVATIVES AND METHOD FOR PRODUCING THE SAME}

The present invention provides various organic synthesis reactions and physiologically active natural products such as Suzuki carbon-carbon coupling reaction using palladium catalyst, 1,2- and 1,4-addition reaction using halogen catalyst, and halogen substitution reaction. The present invention relates to a novel potassium organotrifluoroborate compound having a hydroxy group which can be widely used for the total synthesis of a compound, and a method of preparing the same.

Recently, various carbon-carbon bonding methods using metal catalysts have been reported in the field of organic chemistry. These advances in organometallic chemistry enable the synthesis of terrestrial and marine natural products with very complex structures that could not be made by artificial synthesis in the past. have. In particular, the carbon-carbon coupling reaction using boron discovered by Suzuki and Miyaura professors in Japan is a compound that has a higher natural affinity than a substance using zinc, tin, and magnesium. It is less dangerous to the human body, more stable than the existing reactions such as using water for the reaction conditions, and has an advantage that it is easy to apply to various fields (natural synthesis, medicinal chemistry, polymer synthesis, etc.) Has been very active ( Chem. Rev. 1995 , 95 , 2457; Angew. Chem., Int. Ed. 2001 , 40 , 4544). Suzuki's carbon-carbon coupling reaction proceeds mainly with palladium (Pd) organometallic catalysts. The known reactions start from organoboronic acid or organoboronate esters. However, organic boric acid or organic boron ester is difficult to quantitatively react due to its nature of dimer or trimer, and it is difficult to quantitatively react catechol, pinacol, Since diethanolamine is an expensive ligand, it is difficult to recover it after the reaction, and it is easy to be attacked by Lewis base or other common nucleophiles and cause side reactions. have. Contrary to this, potassium organotrifluoroborate is a very stable compound in air and moisture, and the reaction to obtain it is easily obtained by adding cheap potassium hydrogen fluoride (KHF ₂ ) to organoboronic acid or organoboron ester. There is an advantage. The reactivity in the Suzuki reaction also does not differ so much that the carbon-carbon reaction using potassium organotrifluoroborate is expected to be used in many fields in the future ( Aldrichimica Acta 2005 , 38 , 49; J. Org. Chem. 2003 , 4313; Acc. Chem. Res. 2007 , 40 , 275; Tetrahedron 2007 , 63 , 3623).

Sigma-Aldrich, a leading global reagent manufacturer, manufactures and sells over 30 kinds of potassium organotrifluoroborate, and small and medium sized foreign reagents are also used in combination and pharmaceutical chemicals. Potassium organotrifluoroborate Eventually, the compounds are expected to be widely used in place of organoboronic acid or organoboron esters in Suzuki carbon-carbon coupling reactions. However, compared to the potential of this demand, the types of potassium organotrifluoroborates developed so far are not varied enough to satisfy them. Recently, various derivatives of potassium organotrifluoroborate and easy methods for preparing them have been published, and further studies are still needed ( J. Am. Chem. Soc. 2003 , 125 , 11148; Org. Lett. 2006 , 8 , 75; Org.Lett. 2006 , 8 , 2767; J. Am. Chem. Soc. 2006 , 128 , 9634; J. Org.Chem . 2006 , 71 , 749; J. Org.Chem. 2006 , 71 , 6135; Org. Lett. 2007 , 9 , 821; J. Org.Chem. 2007 , 72 , 3558).

Therefore, the development of new potassium organotrifluoroborate derivatives can be used as a very useful compound for the easy synthesis of sensitive reactants or complex substances in the preparation of various organic compounds and new drug development studies using physiologically active natural products.

Potassium organotrifluoroborate compounds, despite their effectiveness, have the following drawbacks in the production process.

(1) In general, potassium organotrifluoroborate compounds are prepared using relatively expensive organoboronic acids or organoboron esters as starting materials.

(2) In the following Scheme 1, in order to synthesize an organoboronic acid or organoborate ester including an alcohol group, there is a disadvantage in that a complex route of protecting and removing the hydroxy group before the lithium-halogen substitution reaction is removed.

(3) In Reaction Scheme 1, the silyl (silyl: -SiR ₃ ) compounds used to protect the hydroxyl group are relatively expensive compounds, and the synthesis method of potassium organotrifluoroborate through the process of using them as a protecting group is uneconomical.

(4) The organoboronic acid or organoboron ester compound of Scheme 1 has a disadvantage in that it cannot be quantitatively reacted in purification, storage, and reaction using the same because it easily forms a polymer in air.

Scheme 1

Therefore, there has been a demand for the emergence of a method for producing potassium organotrifluoroborate having a hydroxy group easily, inexpensively, and quickly.

It is an object of the present invention to provide a convenient and economical method for preparing the potassium organotrifluoroborate salt compound of Formula 1 in a single reaction without undergoing the separation and purification of the intermediate from the arylhalogen compound having a hydroxy group.

In addition, the present invention is a variety of organic synthesis such as Suzuki carbon-carbon coupling reaction using the Palladium (Pd) catalyst, 1,2- and 1,4-addition reaction using the rhodium (Rh) catalyst, halogen substitution reaction Another object of the present invention is to provide a novel potassium organotrifluoroborate compound having a hydroxyl group which can be widely used for the synthesis of the reaction and bioactive natural products.

In view of the above facts, the present inventors have diligently studied, and as shown in the following Scheme 2, the aryl halogen compound of Formula 2 having a hydroxyl group, which is a hydrogen-primary substituent, is reacted with an organometallic reagent to protect a hydrogen-primary substituent. At the same time, a halogen-lithium substitution reaction is carried out [step A-1], followed by continuous reaction with a borate compound (B (OR ² ) ₃ ) [step A-2], which is used to separate potassium hydrogen fluoride ( KHF ₂ ) or a three-step reaction to react with [Step A-3], or a reaction of the organometallic reagent to a mixture of a compound of Formula 2 and a borate compound (B (OR ² ) ₃ ) [Step A- 4], the potassium organotrifluoroborate compound of Formula 1 was obtained through a two-step reaction step of continuously reacting with potassium hydrogen fluoride (KHF ₂ ), thereby completing the present invention.

Scheme 2

The method for preparing the potassium organotrifluoroborate compound of Formula 1 according to the first aspect of the present invention includes the following preparation steps, more preferably an intermediate, that is, a product of each step, that is, a compound of Formula 3 and Formula 4 The compound proceeds continuously without separation.

a) preparing a compound of Chemical Formula 3 by reacting a compound of Chemical Formula 2 with an organolithium reagent;

b) reacting a compound of Formula 3 with a borate compound of Formula 5 to produce a compound of Formula 4; And

c) reacting a compound of Formula 4 with potassium hydrogen fluoride to prepare a compound of Formula 1.

According to a second aspect of the present invention, a method for preparing a potassium organotrifluoroborate compound represented by Chemical Formula 1 includes the following preparation steps, and more preferably, an intermediate, that is, a compound of Chemical Formula 4, is separated from each step. Proceed continuously.

a) preparing a compound of formula 4 by reacting an organolithium reagent with a mixture of a compound of formula 2 and a borate compound of formula 5; And

b) reacting the compound of Formula 4 with potassium hydrogen fluoride to prepare a compound of Formula 1.

[Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

B (OR ² ) ₃

[In Formulas 1 to 5, Ar is selected from phenylene, biphenylene, naphthylene or anthylene;

R ¹ is independently selected from an alkyl group having 1 to 7 carbon atoms, an alkyloxy group having 1 to 7 carbon atoms, an alkylthiooxy group having 1 to 7 carbon atoms, a hydroxyphenyl group, a hydroxynaphthyl group and a halogen atom;

R ² is selected from an alkyl group having 1 to 7 carbon atoms or a phenyl group;

X is selected from bromine or iodine atom;

m is selected from an integer of 1 to 3;

n is selected from an integer of 0 to 4;

p is selected from an integer of 0-4.]

In another aspect, the present invention provides a novel potassium organotrifluoroborate compound having a hydroxyl group, represented by the following formula (6).

[Formula 6]

[In Formula 6, Ar is selected from phenylene, biphenylene, or naphthylene;

R ¹¹ is independently selected from an alkyl group having 1 to 7 carbon atoms or a halogen atom;

r is selected from an integer of 0 to 2;

q is selected from an integer of 0 to 2.]

As a more specific compound, a novel potassium organotrifluoroborate compound having a hydroxy group included in Formula 6 may be potassium 2-hydroxyphenyltrifluoroborate, potassium 3-hydroxyphenyltrifluoroborate, Potassium 4-hydroxyphenyltrifluoroborate, potassium 4'-hydroxy- [1,1'-biphenyl] -4-trifluoroborate, potassium 6-hydroxy-2-naphthalenetrifluoroborate, potassium 4-hydroxy-3,5-dimethylphenyltrifluoroborate, potassium 4-hydroxy-3-methylphenyltrifluoroborate, potassium 3-chloro-4-hydroxyphenyltrifluoroborate, potassium 2- (hydroxy Hydroxymethyl) phenyltrifluoroborate, potassium 3- (hydroxymethyl) phenyltrifluoroborate, potassium 4- (hydroxymethyl) phenyltrifluoroborate, potassium 2- (2-hydroxyethyl) phenyltriflo Robore Nitrate, potassium 3- (2-hydroxyethyl) phenyltrifluoroborate, potassium 4- (2-hydroxyethyl) phenyltrifluoroborate, and the like.

Hereinafter, the manufacturing method of this invention is demonstrated in detail.

In the preparation method according to the present invention, the potassium organotrifluoroborate salt compound of Formula 1 may be prepared in a single reaction without undergoing the process of separating and purifying the intermediate, and specifically, a three-step process as shown in Scheme 2 above. Or in a two step process. In the three-step process, the hydroxy group of the compound represented by Chemical Formula 2 is protected with an organolithium reagent, the halogen-lithium substitution reaction is carried out, and then sequentially reacted with the borate compound of Chemical Formula 5, followed by potassium hydrogen fluoride and distilled water. Termination to prepare the potassium organotrifluoroborate compound of formula (1). In the second step, the compound of Formula 2 and the borate compound of Formula 5 are mixed, followed by reaction by adding an organic lithium reagent, and subsequently terminated with potassium hydrogen fluoride and distilled water to potassium organotrifluoro of Formula 1 Prepare borate compounds. Compounds of the formula (II) used as raw materials in the production method of the present invention are readily available as known compounds.

As shown in Scheme 2, the production method [Step A] according to the present invention means a single step without undergoing intermediate separation and purification, and includes a three-step or two-step reaction step in detail. Below, a detailed process is explained in full detail.

[3-step reaction process]

[Step A-1]

As the anhydrous solvent used to prepare the compound of Formula 2, a mixed solvent in which a single solvent such as diethyl ether, tetrahydrofuran, hexane, heptane, and two or more solvents are combined. Among them, preferred solvents are diethyl ether, tetrahydrofuran or a mixed solvent of diethyl ether and tetrahydrofuran.

Examples of the organic lithium reagent used for the hydroxy group protection reaction and the halogen-metal substitution reaction include n-butyllithium, sec-butyllithium and tert-butyllithium. Of these, tert-butyllithium is preferable. Usually, the amount of use is in the range of 2 to 5 equivalents, preferably 2.0 to 2.2 equivalents for n-butyllithium and sec-butyllithium and 3.0 to 3.2 equivalents for t-butyllithium. When the amount of organolithium is used less than 2.0 equivalents, the hydroxy group protection reaction is well formed, but the halogen-metal substitution reaction is not completely performed, which ultimately causes a decrease in yield of the desired organotrifluoroborate. On the other hand, the use of excessive organolithium is not good because the by-products such as potassium n-butyltrifluoroborate, potassium sec-butyltrifluoroborate and potassium t-butyltrifluoroborate are obtained together.

The reaction temperature may vary depending on the solvent used, but is usually -78 to -10 ° C, preferably -78 to -40 ° C. The reaction time may vary depending on the reaction temperature and the solvent used. The reaction time is usually 10 minutes to 240 minutes, preferably 30 minutes to 90 minutes.

[Step A-2]

Examples of the borate compound of Formula 5 reacted with Formula 3 include trialkylborate reagents such as trimethylborate (B (OCH ₃ ) ₃ ), triethylborate (B (OCH ₂ CH ₃ ) ₃ ), and tripropylborate (B (OCH ₂ CH ₂ CH ₃ ) ₃ ), triisopropylborate (B (O- ⁱ Pr) ₃ ), triisobutylborate (B (OCH ₂ ^-i Pr) ₃ ), triphenylborate (B (OPh) ₃ ), etc. There is this. Among these, triisopropyl borate is preferable. The amount of the borate compound represented by the formula (5) is usually 0.9 to 3 equivalents, preferably 0.95 to 1 equivalents. When the borate compound is used at less than 0.9 equivalents, the desired organotrifluoroborate yield is low, and when used at more than 3.0 equivalents, it is difficult to obtain a pure target compound by increasing the production of side reaction materials.

The reaction temperature may vary depending on the solvent and the organolithium reagent used, but is usually -78 to 0 ° C. Preferably, the reaction temperature is maintained at -75 ° C when the borate compound of Formula 5 is added and the temperature is gradually decreased from -75 ° C. Respond while teasing. The reaction time is usually 30 minutes to 1 day, and preferably 30 to 90 minutes.

[Step A-3]

Potassium hydrogen fluoride and distilled water were added to the compound of formula 4 to terminate the reaction, and the solvent was distilled off under reduced pressure to completely remove the solvent. The blended mixed solvent is added to dissolve, and celite is used to remove insoluble salts. The filtered acetone is again removed under reduced pressure to obtain a compound of formula 1.

Potassium hydrogen fluoride is normally used in 2 to 10 equivalents, preferably 3 to 5 equivalents. If the amount of potassium hydrogen fluoride is less than 2.0 equivalents, the yield is reduced due to the lack of fluoride element of organotrifluoroborate. This occurs and has a disadvantage in that the purification becomes difficult. However, the pH of the mixed solution is 4 or less, more specifically, pH 1-4. When the pH of the mixed solution exceeds 4, there is a disadvantage in that crystal formation of organotrifluoroborate is not good. The reaction temperature is carried out at 0 ~ 25 ℃, the reaction time is reacted for 10 to 60 minutes.

[2-Step Reaction Process]

[Step A-4]

The compound of formula (2) and the borate compound of formula (5) are dissolved in anhydrous solvent, and an organic lithium reagent is added to carry out alcohol group protection reaction and halogen-lithium substitution reaction simultaneously.

Borate compounds of the formula (5) used in this process include trimethyl borate reagent trimethyl borate, triethyl borate, tripropyl borate, triisopropyl borate, triisobutyl borate, triphenyl borate. Among these, triisopropyl borate is preferable. The amount of trialkyl borate to be used is usually 0.9 to 3 equivalents, preferably 0.95 to 1 equivalents.

Examples of the organic lithium reagent used for the hydroxy group protection reaction and the halogen-metal substitution reaction include n-butyllithium, sec-butyllithium and tert-butyllithium. Of these, tert-butyllithium is preferable. Usually, the amount of use is in the range of 2 to 5 equivalents, preferably 2.0 to 2.2 equivalents for n-butyllithium and sec-butyllithium and 3.0 to 3.2 equivalents for t-butyllithium.

The reaction temperature may vary depending on the solvent and the organolithium reagent used, but is usually -78 to 0 ° C. Preferably, the reaction temperature is maintained at -75 ° C when the organolithium reagent is added and the temperature is gradually lowered from -75 ° C. Reacting. The reaction time is usually 30 minutes to 1 day, and preferably 30 to 90 minutes.

[Step A-3]

Potassium hydrogen fluoride and distilled water were added to the compound of formula 4 to terminate the reaction, and the solvent was distilled off under reduced pressure to completely remove the solvent, and then a single solvent such as anhydrous acetone, anhydrous methanol, anhydrous ethanol, anhydrous acetonitrile, or two or more solvents was removed. The blended mixed solvent is added to dissolve, and celite is used to remove insoluble salts. The filtered acetone is again removed under reduced pressure to obtain a compound of formula 1.

Potassium hydrogen fluoride is normally used in 2 to 10 equivalents, preferably 3 to 5 equivalents. However, the pH of the mixed solution should be 4 or less. The reaction temperature is carried out at 0 ~ 25 ℃, the reaction time is reacted for 10 to 60 minutes.

By using the present invention, the potassium organotrifluoroborate compound having a hydroxy group can be easily and economically produced in a single reaction. In addition, the potassium organotrifluoroborate compound has various organic synthesis reactions and physiologically active natural products such as Suzuki carbon-carbon coupling reaction using palladium catalyst, 1,2- and 1,4-addition reaction using rhodium catalyst, halogen substitution reaction, and the like. It can be widely used for the total synthesis of.

In addition, since the aryl group including a hydroxy group plays an important functional group in the physiologically active component of the flavonoids and marine natural substances of land-based natural, the potassium organotrifluoroborate compound of the formula (1) is a total synthesis and derivative synthesis of natural active ingredients, new drug development It is highly commercially available as a compound to replace the existing unstable organoboronic acid or organoboron ester in various organic synthesis reactions.

Hereinafter, the method of the present invention will be described in detail with reference to Examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited only to these examples.

Example 1 Synthesis of Potassium 2-hydroxyphenyltrifluoroborate (3-Step Process)

Under nitrogen conditions 220 mg (1.0 mmol) of 2-iodinephenol are dissolved in 8 mL of anhydrous tetrahydrofuran and the temperature is maintained at -78 ° C. 1.77 mL (1.7 M pentane solution, 3 equivalents) of tert-butyllithium is slowly added dropwise for 10 minutes and further reacted at the same temperature for 30 minutes. 188 mg (1.0 mmol) of triisopropylborate was slowly added dropwise for 15 minutes, and the reaction was heated to -30 ° C over 1 hour for reaction. 273 mg (3.5 mmol, 3.5 equivalents) of potassiumhydrogen fluoride and 4 mL of distilled water are added to terminate the reaction, and the temperature is raised to room temperature, followed by vigorous stirring. After 30 minutes, all solvents are removed by distillation under reduced pressure and the water is removed completely by high vacuum. The residue is taken up in 8 mL of anhydrous acetone and the celite is used to remove the insoluble salts. The filtered acetone is concentrated and precipitated by the addition of 10 mL of ether (Et ₂ O). The obtained white crystals were filtered and dried to obtain 154 mg (yield = 77%) of potassium 2-hydroxyphenyltrifluoroborate.

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 7.37 (q, 1H, -OH, J = 9.1 Hz), 7.11 (dd, 1H, J = 7.0, 1.0 Hz), 6.91 (td, 1H, J = 7.6, 1.6 Hz), 6.58 (t, 1H, J = 7.1 Hz), 6.49 (d, 1H, J = 8.0 Hz).

^{13 C NMR (126 MHz, DMSO-} d 6) δ 159.9, 133.6, 127.6, 119.0, 114.0.

Example 2 Synthesis of Potassium 2-hydroxyphenyltrifluoroborate (Two Step Process)

Under nitrogen conditions, 220 mg (1.0 mmol) of 2-iodinephenol and 188 mg (1.0 mmol) of triisopropylborate are dissolved in 8 mL of anhydrous tetrahydrofuran and the temperature is maintained at -78 ° C. 1.77 mL of tert-butyllithium (1.7 M pentane solution, 3 equivalents) was slowly added dropwise for 10 minutes, and further reacted at the same temperature for 40 minutes, and then the temperature was gradually raised to -30 ° C. over 1 hour. 273 mg (3.5 mmol, 3.5 equivalents) of potassiumhydrogen fluoride and 4 mL of distilled water are added to terminate the reaction, and the temperature is raised to room temperature, followed by vigorous stirring. After 30 minutes, all solvents are removed by distillation under reduced pressure and the water is removed completely by high vacuum. The residue is taken up in 8 mL of anhydrous acetone and the celite is used to remove the insoluble salts. The filtered acetone is concentrated and precipitated by the addition of 10 mL of ether (Et ₂ O). The white crystals obtained were filtered and dried to obtain 130 mg (yield = 65%) of the title compound.

Example 3 Synthesis of Potassium 3-hydroxyphenyltrifluoroborate (3-Step Process)

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 220 mg (1.0 mmol) of 3-iodinephenol, and the resultant was purified to obtain 196 mg (yield = 98%) of the title compound.

¹ H NMR (500 MHz, CD ₃ OD) δ 7.04 (t, 1H, J = 7.5 Hz), 6.98 (m, 2H), 6.61 (dd, 1H, J = 7.5, 2.5 Hz).

¹³ C NMR (126 MHz, CD ₃ OD) δ 155.8, 127.9, 122.8, 117.9, 113.0.

Example 4 Synthesis of Potassium 3-hydroxyphenyltrifluoroborate (2-Step Process)

The reaction was carried out in the same manner as in Example 2, except that 2-iodinephenol was used in place of 220 mg (1.0 mmol) of 3-iodinephenol, and the residue was purified to yield 172 mg (yield = 86%) of the title compound.

Example 5 Synthesis of Potassium 4-hydroxyphenyltrifluoroborate (3-Step Process)

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 220 mg (1.0 mmol) of 4-iodinephenol, and the resultant was purified to obtain 196 mg (yield = 98%) of the title compound.

¹ H NMR (500 MHz, Acetone- d ₆ + DMSO- d ₆ ) δ 7.98 (br s, 1H), 7.29 (d, 2H, J = 7.5 Hz), 6.60 (d, 2H, J = 8.0 Hz).

¹³ C NMR (126 MHz, Acetone- d ₆ + DMSO- d ₆ ) δ 155.6, 132.7, 113.5.

Example 6 Synthesis of Potassium 4-hydroxyphenyltrifluoroborate (Two Step Process)

The reaction was carried out in the same manner as in Example 2, except for replacing 2-iodine phenol with 220 mg (1.0 mmol) of 4-iodine phenol, to obtain 146 mg (yield = 73%) of the title compound.

Example 7 Synthesis of Potassium 4-hydroxyphenyltrifluoroborate (3-Step Process)

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used instead of 173 mg (1.0 mmol) of 4-bromophenol, and the resultant was purified to give 122 mg (yield = 61%) of the title compound.

Example 8 Synthesis of Potassium 4 ^, -hydroxy- [1,1 ^, -biphenyl] -4-trifluoroborate

2-iodophenol ^{4-bromo- [1,1-biphenyl],} and the reaction is then purified in the same manner as Example 1 except that by replacing -4-ol 249.1 mg (1.0 mmol ) 102 mg (yield = 37%) of the title compound were obtained.

¹ H NMR (500 MHz, Acetone- d ₆ + DMSO- d ₆ ) δ 8.99 (br s, 1H), 7.52 (d, 2H, J = 8.0 Hz), 7.42 (d, 2H, J = 8.5 Hz), 7.32 (d, 2H, J = 7.5 Hz), 6.86 (d, 2H, J = 8.5 Hz).

¹³ C NMR (126 MHz, Acetone- d ₆ + DMSO- d ₆ ) δ 157.0, 137.7, 137.7, 133.6, 132.3, 127.6, 124.4, 115.7.

Example 9 Synthesis of Potassium 4 ^, -hydroxy- [1,1 ^, -biphenyl] -4-trifluoroborate

The reaction was carried out in the same manner as in Example 1 except that 2-iodinephenol was used by replacing 296.1 mg (1.0 mmol) of 4 ^, -iodine- [1,1 ^, -biphenyl] -4-ol, and then purified. 238 mg (yield = 86%) of the title compound were obtained.

Example 10 Synthesis of Potassium 6-hydroxy-2-naphthalenetrifluoroborate

The reaction was carried out in the same manner as in Example 1, except for replacing 2-iodinephenol with 223 mg (1.0 mmol) of 6-bromo-2-naphthol, and then purifying 190 mg (yield = 76%) of the title compound. Got.

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 8.19 (s, 1H), 7.84 (s, 1H), 7.60 (d, 1H, J = 3.7 Hz), 7.59 (d, 1H, J = 8.1 Hz) , 7.43 (d, 1H, J = 8.1 Hz), 7.07 (d, 1H, J = 2.4 Hz), 6.99 (dd, 1H, J = 8.8, 2.5 Hz).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 154.0, 134.1, 131.6, 130.1, 129.3, 128.8, 123.7, 116.8, 108.8.

Example 11 Synthesis of borate in a triple potassium 4-hydroxy-3,5-dimethylphenyl

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used by replacing 201 mg (1.0 mmol) of 4-bromo-2,6-dimethylphenol and purified to give 148 mg of the title compound (yield = 65%).

^{1 H NMR (500 MHz, Acetone-} d 6) δ 6.89 (s, 2H), 6.33 (s, 1H), 2.02 (s, 6H).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 151.2, 132.3, 121.1, 114.9, 16.0.

Example 12 Synthesis of Potassium 4-hydroxy-3-methylphenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 187 mg (1.0 mmol) of 4-bromo-2-methylphenol, and the resultant was purified to give 163 mg of the title compound (yield = 76%). )

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.36 (s, 1H), 7.19 (s, 1H), 7.12 (d, 1H, J = 7.5 Hz), 6.57 (d, 1H, J = 7.5 Hz) , 2.15 (s, 3 H).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 153.4, 134.6, 130.2, 121.3, 113.2, 15.7.

Example 13 Synthesis of Potassium 4-hydroxy-3-methylphenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 234 mg (1.0 mmol) of 4-iodine-2-methylphenol, and the residue was purified to give 208 mg of the title compound (yield = 97%). Got.

Example 14 Synthesis of Potassium 3-chloro-4-hydroxyphenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 207.5 mg (1.0 mmol) of 4-bromo-2-chlorophenol, and the resultant was purified to give 209 mg of the title compound (yield = 89%). )

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.89 (br s, 1H), 7.36 (s, 1H), 7.22 (d, 1H, J = 7.5 Hz), 6.77 (d, 1H, J = 7.5 Hz ).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 150.5, 132.9, 131.3, 118.7, 115.3.

Example 15 Synthesis of Potassium 2- (hydroxymethyl) phenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was replaced with 187 mg (1.0 mmol) of 2-bromo-benzyl alcohol, and then 128 mg (yield = 60%) of the title compound was purified. Got it.

^{1 H NMR (500 MHz, Acetone-} d 6) δ 7.54 (m, 1H), 7.11 (m, 1H), 7.01 (m, 2H), 4.64 (s, 2H), 3.63 (br s, 1H).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 145.2, 132.6, 127.3, 125.4, 125.3, 65.8.

Example 16 Synthesis of Potassium 3- (hydroxymethyl) phenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 187 mg (1.0 mmol) of 3-bromo-benzyl alcohol, to purify 178 mg (yield = 83%) of the title compound. Got it.

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.45 (s, 1H), 7.36 (t, 1H, J = 4.5 Hz), 7.07 (d, 2H, J = 4.5 Hz), 4.53 (d, 2H, J = 6.0 Hz), 3.82 (t, 1H, J = 6.0 Hz).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 139.8, 130.6, 130.5, 126.3, 124.1, 65.2.

Example 17 Synthesis of Potassium 4- (hydroxymethyl) phenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 187 mg (1.0 mmol) of 4-bromo-benzyl alcohol, to purify 193 mg (yield = 90%) of the title compound. Got it.

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.44 (d, 2H, J = 7.5), 7.10 (d, 2H, J = 7.5 Hz), 4.54 (d, 2H, J = 6.0 Hz), 3.83 ( t, 1H, J = 6.0 Hz).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 139.0, 131.6, 125.2, 64.8.

Example 18 Synthesis of Potassium 2- (2-hydroxyethyl) phenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was replaced with 201 mg (1.0 mmol) of 2-bromo-phenethyl alcohol, and then purified to give 116 mg of the title compound (yield = 51%). )

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.43 (m, 1H), 6.97 (m, 2H), 6.88 (m, 1H), 3.90 (t, 2H, J = 5.5 Hz), 2.65 (t, 2H, J = 5.5 Hz).

¹³ C NMR (126 MHz, Acetone- d ₆ ) δ 143.2, 131.4, 126.0, 125.4, 124.7, 61.7, 34.1.

Example 19 Synthesis of Potassium 3- (2-hydroxyethyl) phenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was replaced with 201 mg (1.0 mmol) of 3-bromo-phenethyl alcohol, and the resultant was purified to give 155 mg of the title compound (yield = 68%). Got.

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.37 (s, 1H), 7.33 (d, 1H, J = 7.5 Hz), 7.04 (t, 1H, J = 7.5 Hz), 6.94 (d, 1H, J = 7.5 Hz), 3.71 (q, 2H, J = 7.0 Hz), 3.58 (t, 1H, J = 5.5 Hz), 2.75 (t, 2H, J = 7.0 Hz).

^{13 C NMR (126 MHz, Acetone-} d 6) δ 136.8, 132.5, 129.6, 126.6, 126.2, 63.8, 40.2.

Example 20 Synthesis of Potassium 4- (2-hydroxyethyl) phenyltrifluoroborate

The reaction was carried out in the same manner as in Example 1, except that 2-iodinephenol was used in place of 201 mg (1.0 mmol) of 4-bromo-phenethyl alcohol (166 mg, yield = 73%). Got.

¹ H NMR (500 MHz, Acetone- d ₆ ) δ 7.40 (d, 2H, J = 7.5 Hz), 6.98 (d, 2H, J = 7.5 Hz), 3.70 (q, 2H, J = 7.5 Hz), 3.54 (t, 1H, J = 5.5 Hz), 2.74 (t, 2H, J = 7.5 Hz).

¹³ C NMR (126 MHz, Acetone d ₆ ) δ 135.9, 131.8, 127.2, 63.8, 39.9.

Claims (9)

a) preparing a compound of Chemical Formula 3 by reacting a compound of Chemical Formula 2 with an organolithium reagent; b) reacting a compound of Formula 3 with a borate compound of Formula 5 to produce a compound of Formula 4; And c) reacting a compound of Formula 4 with potassium hydrogen fluoride to prepare a compound of Formula 1; A method for preparing a potassium organotrifluoroborate compound of Formula 1, comprising: proceeding continuously without separating intermediates that are products of each step. [Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5] B (OR ² ) ₃ [In Formulas 1 to 5, Ar is selected from phenylene, biphenylene, naphthylene or anthylene; R ¹ is independently selected from an alkyl group having 1 to 7 carbon atoms, an alkyloxy group having 1 to 7 carbon atoms, an alkylthiooxy group having 1 to 7 carbon atoms, a hydroxyphenyl group, a hydroxynaphthyl group and a halogen atom; R ² is selected from an alkyl group having 1 to 7 carbon atoms or a phenyl group; X is selected from bromine or iodine atom; m is selected from an integer of 1 to 3; n is selected from an integer of 0 to 4; p is selected from an integer of 0-4.] a) preparing a compound of formula 4 by reacting an organolithium reagent with a mixture of a compound of formula 2 and a borate compound of formula 5; And b) reacting the compound of Formula 4 with potassium hydrogen fluoride to prepare a compound of Formula 1; A method for preparing a potassium organotrifluoroborate compound of Formula 1, comprising: proceeding continuously without separating intermediates that are products of each step. [Formula 1]

[Formula 2]

[Formula 4]

[Formula 5] B (OR ² ) ₃ [In Formula 1 to Formula 2, Formula 4 to Formula 5, Ar is selected from phenylene, biphenylene, naphthylene or anthylene; R ¹ is independently selected from an alkyl group having 1 to 7 carbon atoms, an alkyloxy group having 1 to 7 carbon atoms, an alkylthiooxy group having 1 to 7 carbon atoms, a hydroxyphenyl group, a hydroxynaphthyl group or a halogen atom; R ² is selected from an alkyl group having 1 to 7 carbon atoms or a phenyl group; X is selected from bromine or iodine atom; m is selected from an integer of 1 to 3; n is selected from an integer of 0 to 4; p is selected from an integer of 0-4.] The method according to claim 1 or 2, The organolithium reagent is a method for preparing the potassium organotrifluoroborate compound of Formula 1, characterized in that 2 to 5 equivalents of one selected from n-butyllithium, sec-butyllithium, or tert-butyllithium are used. . The method according to claim 1 or 2, The borate compound of Formula 5 is trimethyl borate (B (OCH ₃ ) ₃ ), triethyl borate (B (OCH ₂ CH ₃ ) ₃ ), tripropyl borate (B (OCH ₂ CH ₂ CH ₃ ) ₃ ), triiso 0.9 to 3 equivalents of one selected from propylborate (B (O- ⁱ Pr) ₃ ), triisobutylborate (B (OCH ₂ ^-i Pr) ₃ ), or triphenylborate (B (OPh) ₃ ) Method for producing a potassium organotrifluoroborate compound of Formula 1, characterized in that. The method according to claim 1 or 2, The potassium hydrogen fluoride is a method for producing a potassium organotrifluoroborate compound of Formula 1, characterized in that 2 to 10 equivalents are used so that the pH of the reaction solution is 4 or less. The method according to claim 1 or 2, After preparing the compound of Formula 1, further comprising the step of purifying the compound of Formula 1 using one or two or more mixed solvents selected from anhydrous acetone, anhydrous methanol, anhydrous ethanol, an acetonitrile, or anhydrous ether. Method for producing a potassium organotrifluoroborate compound of formula (1) characterized in that. delete delete delete